Discovery of potent and selective small molecule NPY Y5 receptor antagonists

Imadul Islam; Dale Dhanoa; John Finn; Ping Du; Mary W Walker; John A Salon; Jack Zhang; Charles Gluchowski

doi:10.1016/s0960-894x(02)00287-1

Discovery of potent and selective small molecule NPY Y5 receptor antagonists

Bioorg Med Chem Lett. 2002 Jul 8;12(13):1767-9. doi: 10.1016/s0960-894x(02)00287-1.

Authors

Imadul Islam¹, Dale Dhanoa, John Finn, Ping Du, Mary W Walker, John A Salon, Jack Zhang, Charles Gluchowski

Affiliation

¹ Synaptic Pharmaceutical Corporation, 215 College Road, Paramus, NJ 07652. USA.

PMID: 12067557
DOI: 10.1016/s0960-894x(02)00287-1

Abstract

The discovery of a new class of sulfonamide NPY Y5 receptor antagonists is described. Optimization of this series led to the identification of compounds with high affinity for the hY5 subtype and excellent selectivity over the other NPY receptor subtypes. The SAR for this series was examined and a model for understanding the ligand-receptor interactions was developed.

MeSH terms

Animals
COS Cells
Histidine / chemistry
Humans
Membrane Proteins / chemistry
Membrane Proteins / metabolism
Models, Molecular
Mutagenesis, Site-Directed
Protein Structure, Secondary
Radioligand Assay
Receptors, Neuropeptide Y / antagonists & inhibitors*
Receptors, Neuropeptide Y / chemistry*
Receptors, Neuropeptide Y / metabolism
Stereoisomerism
Structure-Activity Relationship
Sulfonamides / chemistry*
Sulfonamides / metabolism
Sulfonamides / pharmacology*

Substances

Membrane Proteins
Receptors, Neuropeptide Y
Sulfonamides
neuropeptide Y5 receptor
Histidine